Nivolumab active against dMMR/MSI-H colorectal cancer
medwireNews: Patients with pretreated metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer respond well to treatment with the programed cell death protein 1 (PD-1) immune checkpoint inhibitor nivolumab, phase II trial data show.
“These results suggest that nivolumab could be a new treatment option in patients with dMMR/MSI-H metastatic colorectal cancer, as reflected by the recent inclusion of nivolumab in the National Comprehensive Cancer Network treatment guidelines for this population,” Michael Overman (The University of Texas MD Anderson Cancer Center, Houston, USA) and co-investigators remark.
Of the 74 adults with histologically confirmed recurrent or metastatic colorectal cancer included in the CheckMate 142 trial, 23 (31%) had an investigator-assessed objective response to treatment with nivolumab 3 mg/kg every 2 weeks at a median follow-up of 12 months.
In addition, 51 (69%) of the patients, who were recruited from 31 sites in eight countries, had disease control for 12 weeks or longer.
At the time of data analysis, following a 2-year enrolment period, the median duration of response had not been reached; all 23 responders were alive, and eight (35%) had responses lasting at least 12 months.
The median progression-free survival (PFS) was 14.3 months, with a 12-month PFS rate of 50% and a 12-month overall survival rate of 73%.
Overman and team note that responses occurred regardless of tumor PD-L1 expression, BRAF or KRAS mutation status, and clinical history of Lynch syndrome, which suggests that these variables could not be used as biomarkers for response in this population.
The researchers also found that nivolumab was associated with clinically meaningful improvements in patient-reported functioning, symptoms, and global quality of life, from as early as week 13 and lasting until at least week 37.
The drug was well tolerated by patients; 15 (21%) reported treatment-related adverse events, most commonly increased concentrations of lipase (8%) and amylase (3%).
Commenting on the findings published in The Lancet Oncology, Francesco Sclafani, from The Royal Marsden NHS Foundation Trust in Sutton, UK, says: “The results of the CheckMate 142 trial, which are broadly consistent with previous findings of studies of pembrolizumab, are notable in view of the generally poor prognosis of patients with dMMR/MSI-H metastatic colorectal cancer.
“Therefore, despite the small numbers and non-randomised study design, the results establish a new treatment option in this setting and confirm that MMR/MSI testing can no longer be considered as an ad-hoc screening procedure for genetic susceptibility or treatment selection in early-stage tumours, but should now be routinely offered to all patients with metastatic colorectal cancer.”
Overman et al conclude: “Ongoing studies are exploring the combination of nivolumab with other immunotherapies in patients with dMMR/MSI-H metastatic colorectal cancer.”
By Laura Cowen
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